Comparison of Estradiol Concentrations Between Transgender Women Taking Oral Estrogen-Based Gender-Affirming Hormone Therapy With and Without Concurrent Bictegravir/Tenofovir Alafenamide/Emtricitabine

Abstract

Purpose:

Drug–drug interaction (DDI) concerns between estrogen-based gender-affirming hormone therapy (E-GAHT) and antiretroviral therapy (ART) remain poorly characterized. We assessed serum estradiol concentrations in transgender women with HIV on E-GAHT and bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) compared with transgender women without HIV on E-GAHT.

Methods:

This parallel-group study (2023/24) included transgender women with and without HIV taking E-GAHT (≥2 mg/day oral 17-β estradiol plus anti-androgen therapy) for ≥3 months. Transgender women with HIV were on suppressive ART for ≥6 months and taking or switched to BIC/TAF/FTC. Estradiol concentrations were collected at month 2 pre-dose and then 1, 2, 3, 4, 6, 8, and 24 h post-dose. Medians of estradiol maximum concentration (C_max), time to C_max (T_max), and area under the curve (AUC) were compared between groups using Wilcoxon rank-sum test. The proportions of estradiol 4 h concentration (C_4h) within the target range (200–735 pmol/L) were compared using Fisher’s exact test.

Results:

Among 25 participants (10 on BIC/TAF/FTC and 15 controls), the median oral 17-β estradiol dose was 4 mg/day (range 2–8 mg). Median estradiol C_max and T_max were 357.5 pmol/L and 1.5 h for BIC/TAF/FTC users and 262 pmol/L and 4 h for controls (p = 0.12 and p = 0.13, respectively). AUCs were similar between groups (p = 0.24). Of the transgender women with HIV 80% had estradiol C_4h within the target range, compared with 53% of transgender women without HIV (p = 0.23).

Conclusions:

Estradiol concentrations were comparable between groups indicating a low likelihood of a relevant DDI, but this conclusion is limited by the small sample size.